The clinical management of patients with cancer does not entail a one size fits all approach. In fact, studies of the genomic landscape of human cancers have demonstrated that cancers can have a multitude of mutations, a subset of which may be actionable with current drugs. Thus, the personalization of therapy for cancer will require molecular characterization of unique and shared genetic aberrations. In particular, patients who have advanced / refractory cancer and are candidates for clinical trials could potentially benefit by identifying eligibility for targeted drugs based on the actionable genesin their specific tumor. Growing technological advances in genomic sequencing has now made it possible to consider the use of sequence data in a clinical setting. Thus, the translation of high throughput sequencing would support a personalized strategy for cancer. However, the translation of clinical sequencing bears unique challenges including identifying patients who could benefit, developing informed consent and human subjects protections, outlining measurable outcomes, interpreting what results should be reported and validated, and how results should be reported. This proposal brings together expertise at the University of Michigan including clinical oncology, cancer genetics, genomic science/bioinformatics, clinical pathology, social and behavioral sciences, and bioethics in order to implement this clinical cancer sequencing project. We have focused our clinical sequencing effort on sarcomas and other rare cancers as this is an area of clinical strength at Michigan. Three integrated Projects have the following themes: Project 1) Clinical Genomic Study will identify patients with advanced or refractory sarcoma or rare cancers who are eligible for clinical trials, consent them to the study obtain biospecimens (tumor tissue, germline tissue), store clinical data, and assemble a multi-disciplinary Sequencing Tumor Board to deliberate on return of actionable or incidental genomic results; Project 2) Sequencing & Analysis will process biospecimens and perform comprehensive sequencing and analysis of tumors to identify point mutations, copy number changes, rearrangements/gene fusions, and aberrant gene expression under CLIA/CAP guidelines; Project 3) Ethics & Psychosocial Analysis will evaluate the clinician and patient response to the informed consent process, delivery of genomic sequence results, and use of genomic results.